Diagnosis of the Acute Attack
The presence of an acute attack must be confirmed in the laboratory. If not, patients may be treated unnecessary and often enter a cycle of repeated admission and treatment for a condition they do not have.
Consult the following pages for details: Proving porphyria: patients with suggestive symptoms and Acute symptoms in porphyria.
Initial Investigations
Take a careful drug history. Exclude, by a careful history and examination, any other problem which may require specific attention. Check sodium, potassium, urea and creatinine. In severe cases, check calcium and magnesium as well.
Therapeutic Intervention
Removal of precipitating factors
Administration of any drug not known to be absolutely safe in porphyria must immediately be stopped. Other potentially complicating factors, such as infection, must be treated.
Analgesia
The pain of the acute attack is very severe. Frequent, high doses of opiate analgesics are usually necessary. We recommend pethidine in doses of 50, 75 or 100 mg given hourly, 2-hourly or 4-hourly. Though some patients may settle with intramuscular doses given four hourly; others may require pethidine intravenously two hourly or hourly. Typically the pain recurs after several hours, leading to appeals for more pethidine. There is no risk of addiction since the acute attack of porphyria is short-lived. A common error is to give too little pethidine, or to label patients too easily as histrionic or addicted.
Fluid therapy
Most patients are dehydrated as a result of nausea, vomiting, poor fluid intake and renal dysfunction. They are also at risk of severe hyponatraemia. They should therefore not receive intravenous dextrose alone. The recommended fluid is normal saline with five percent dextrose.
Specific therapy
The only uniformly effective therapy is haem arginate. This is highly effective in aborting the acute attack, but requires some effort to obtain and is expensive. See Haem arginate for the acute attack of porphyria. Older texts recommend large amounts of carbohydrate as a suppressive therapy for porphyria. The evidence for this is weak and, for any but the mildest attack, haem arginate should be given.
Therapy for Specific Complications of the Acute Attack
Hypertension and tachycardia
These are usually mild and require no specific therapy. If necessary, a non-specific beta blocker such as propranolol is efficacious. In the rare patient with a severe adrenergic crisis, treatment with intravenous magnesium sulphate and combined alpha- and beta-adrenergic blockade may be helpful.
Seizures
These are occasionally due to the porphyria itself, but are often secondary to hyponatraemia. Seizures may also arise in response to large doses of intravenous pethidine, and are often preceded by myoclonic jerks. Seizures should be terminated with intravenous clonazepam 1 mg or diazepam 5-10 mg; clonazepam 0.5 mg bd will prevent further seizures.
Psychosis
True psychosis in response to the acute attack is rare. Phenothiazines such as chlorpromazine are suitable for its control.
Hyponatraemia
Mild degrees of hyponatraemia are treated with intravenous infusions of normal saline. Severe hyponatraemia, particularly if accompanied by confusion or seizures, should be partially corrected with hypertonic saline, taking the usual precautions to prevent over-correction and too-rapid correction. Severe hyponatraemia appears to result from excessive renal sodium losses rather from inappropriate ADH secretion, and fluid restriction is therefore inappropriate.
Paralysis
If haem arginate has not already been commenced, it must be administered as an absolute emergency. The patient should be carefully monitored for the onset of respiratory weakness, preferably in an intensive care unit. Any suggestion of respiratory insufficiency requires immediate intubation and positive pressure ventilation. The motor neuropathy of porphyria is fully reversible. However, as with any other axonal neuropathy, recovery is slow. Ventilation may have to be continued for up to 16 weeks and full recovery may require many months. It is always worthwhile to continue with ventilation, as eventual recovery can be expected.